Exposure Science and Its Places in Environmental Health Sciences and Risk Assessment: Why Is Its Application Still an Ongoing Struggle in 2014?

EDITORIAL Exposure science and its places in environmental health sciences and risk assessment: why is its application still an ongoing struggle in 2014?

Journal of Exposure Science and Environmental Epidemiology (2015) microenvironmental, and receptor activity information do not 25, 1–3; doi:10.1038/jes.2014.59 readily lead to accurate risk assessment or management of a toxicant.10 Thus, a valuable resource has a major deficiency: the lack of personal exposure monitoring and detailed activity/ In 2010, I wrote that “exposure leads to the dose that makes the behavior information, especially for individuals with the highest poison,” to augment Paracelsus’ famous statement.1,2 The concept risks for exposure and for adverse health effects, since biomarker has, however, been at the heart of the field since Wayne Ott3 measurements are not readily matched with actual exposure noted that exposure requires “contact” with a chemical, physical intensity, frequency, duration, or route. Unfortunately, no other or biological agent. Unfortunately, exposure science today still agency has been able to fill in the research gaps due to financial contributes only a minor increment to ongoing environmental constraints. health research in comparison to toxicology, and is only beginning The “exposome” concept took the idea of biomonitoring to a to make real inroads in the area of primary prevention approaches potentially new level by proposing the plausibility of using “-omic” used by engineers and architects to reduce toxicant exposures in tools to assess internal exposures and early markers of disease. our foods, consumer products, cars we drive, and the homes we At the same time, it inadvertently relegated external markers live in. of exposure to secondary status by emphasizing the use I maintain that the continued lack of sufficient appreciation of of biomarkers.11 This was eventually modified to include external exposure science is due to the overemphasis on the hazard markers in order to address the need for intervention in situations component of risk assessment/risk management. The imbalance where one can mitigate the exposure.12,13 The recently started between exposure and hazard in the evaluation of potential Human Early-Life Exposome Project will use both approaches to toxicant risk was quite evident in the first NRC risk assessment evaluate the early-life “exposome”.14 report published ~ 31 years ago (The Red Book4). It was still The neglect of exposure science must not persist, especially in evident in the Silver Book.5 Fortunately, the Silver Book did light of the fact that the public wants more realistic and better risk emphasize simultaneous evaluation of exposure and effects in information. Thus, there is a need to collect data for both external problem formulation. We need to revisit the Integrated Risk and internal markers of exposures, based upon the principles used Information System process to take more advantage of our current with old and new tools, for example, sensors and biomonitoring capabilities in exposure assessment (science)6. We must always that quantify short- and long-term exposures. In each case, the keep in mind that if there is little or no exposure then there is intensity of exposure still cannot be accurately characterized no meaningful dose! without understanding human behavior and activity patterns, a Mention was made in the Silver Book of the Food Quality major requirement that differentiates exposure measurement/ Protection Act of 1996, which had a directive to examine modeling from environmental toxicant risks. cumulative and aggregate risk and led to modeling and The 2012 NRC report, Exposure Science in the 21st Century, The measurement studies on aggregate and cumulative exposures.7 Gold Book,15 built upon the process continuum that the The EPA did, actually, conduct such studies for pesticides, but their environmental health science field has used to define the basic work was abruptly interrupted by the misplaced controversy over principles, and places exposure measurement and modeling design the Children’s Environmental Exposure Research Study. To science as a core discipline that bridges sources with health date, EPA exposure research has not been able to effectively outcomes. The Gold Book made a number of recommendations recover from the fallout, though well-articulated criteria and about the need for exposure science research and its use in policy administrative safeguards for human studies have been published decision making and implementation.15 In addition, it made by the Agency. recommendations about the need for simple sensors, and for the Some say that there has, in fact, been an uptick in exposure engagement of communities at risk. characterization through the more common application of The federal agencies are beginning to coordinate efforts on biomonitoring.8 The National Health and Nutrition Examination exposure science at the national level, a welcomed move forward. Survey program,9 started by the CDC and now mimicked by I attended an EPA summit on Exposure in April 2014 and it was others, has provided substantial amounts of data, and population- good to hear and see that EPA wants to implement many of the based analyses on the internal exposures of the US population ideas presented in Exposure Science in the 21st Century and to many toxicants. They, and others, deserve applause for these continue a dialog with 18 other federal agencies on exposure efforts. Unfortunately, there are still many gaps in our ability to science. However, the financial investment in exposure science accurately interpret these data since there are too few, if any, research still lags. companion measurements of external exposure made by the CDC One critical problem remains. It is that exposure science is still to accompany the biomonitoring measurements. One must not sufficiently recognized as a necessary first step toward understand that a single biomarker measurement can only addressing a suspected environmental health issue. Further, it indicate that a person has been exposed; however, a negative seems that reviewers for health research granting agencies result does not preclude exposure, due to clearance and continue to first focus on a suspected or actual health outcome. metabolic considerations. Moreover, biomarker measurements While that is a suitable approach for an old or known problem that are not complemented by pertinent environmental, area of concern, for others it is like looking for a dime under the Editorial 2 lamp post when the dime is more than 6 feet way from the lighted transport on- and off-site. There was discussion at the work- area. In science you do not always get the right answer or the shop about monitoring of air, water, etc., but very little on most important answer with the first hypothesis. Exposure human exposure monitoring. The recommendations from both science, when implemented properly, can ensure that a health documents tried to address exposure, but primarily as it relates outcome hypothesis is well grounded in reality. The process to health effects, which remain ill defined except for some outlined by the continuum must be used as a guide for health worker populations. I suggest that all stakeholders read the PM 1,15 science research and applications. Thus, one must first committee charge, or at least the summaries for all four reports, “ ” determine the contaminant(s) and sources of greatest concern, to better understand how to systematically address the and then determine which routes of contacts would be of greatest issues on exposure and health for UNG that were presented by concern to health. However, one cannot stop there. The next step, Adgate et al.18 “ ” which is often weakly addressed through guesses, is the We see similar compartmentalization and fragmented research “ ” examination of the contacts that lead to actual acute or chronic on other issues. An important example involves consumer exposures of concern for health. The completion of exposure products containing engineered nanomaterials. The first questions science measurement and modeling projects can guide the that need to be addressed are: Is there any exposure to those development of hypotheses for health effects studies (epidemiol- nanomaterials and, if so, which components, amounts and forms, ogy) and risk characterization that support regulations and 20 strategies to reduce or eliminate contacts and exposures that and for what uses? There are many other examples of situations increase the risk of disease. and conditions that demand better exposure characterizations. In the late 1990s environmental health sciences actually Another example is phthalates. I have been on a Consumer embraced the idea of first characterizing exposure to address an Product Safety Commission (CPSC) panel since about 2010 that is issue within the recommendations made by the NRC committee addressing the impact of phthalates in toys and/or personal care on PM, and their implementation.16,17 One of the important first products on children and women of child-bearing age. The major fi steps in obtaining a better understanding of exposure to the nding is that although we understand the toxicity of many phthalates a major gap in knowledge is quantitative information newly regulated pollutant PM2.5 was to collect data on human on dominant routes of exposure and personal activities (e.g., food contact with ambient air fine particulate matter (PM2.5). The committee recommended, and various organizations (e.g., EPA) ingestion). These data are needed to place phthalate exposures committed, the funds for research needed to quantify “contacts of from toys, etc., into a proper context. concern” before completing new Epidemiological studies (see I could provide more examples, but it is clear that the “ready, Table 5.1 in NRC 1998,16 The Committee’s Research Investment shoot, aim” approach is all too common and inadequate. We in Portfolio: Timing and Estimated Costs (5 $ million/year in 1998 the exposure science community know that merely combining dollars) or Recommended Research on Particulate Matter). This environmental concentration measurements with hazard does not was a logical and scientifically defensible plan. It was stated on provide estimates of actual or even potential human exposures. page 101 of the report that: We must find effective ways to share this knowledge with our colleagues in engineering, biomedicine and toxicology in order to …the committee's research plans for human exposure get a better handle on “contact” with chemicals and then assessment appear first, front-loaded into the early years of exposure. Thus, it is incumbent upon agencies, academia and the portfolio, because there is an urgent need to characterize industry to conduct meaningful exposure studies to fill informa- actual exposures of potentially susceptible persons to tion gaps. I hope these issues are addressed by the government particulate matter and to characterize the biological conse- and other stakeholders, including the Interagency Task Force on quences of those exposures. Methods are already in hand to Exposure Science. assess personal exposures to particulate matter and their outcomes, but little investigation has been done or is yet planned by EPA to investigate the particulate-matter exposures CONFLICT OF INTEREST of susceptible persons, …Further, there is a serious lack of The author declares no conflict of interest. understanding of the relationship of concentrations measured at fixed outdoor monitoring sites with the actual personal Paul J. Lioy1,2,3 exposures of such individuals. Such gaps in knowledge should 1 be addressed immediately in a 3-year program beginning Deputy Editor-in-Chief, Journal of Exposure Science and Environ- in 1998. mental Epidemiology; 2Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA and The results from the recommended studies led to both better 3Rutgers Environmental and Occupational Health Sciences Institute epidemiological and toxicological investigations, and a tightening 17 (EOHSI), Rutgers University, Piscataway, NJ 08854, USA of the PM2.5 standard. The type of structure and process used E-mail: [email protected] to recommend and conduct research on a specific environmental health issue, such as that for particulate matter, does not exist today, but should. REFERENCES A current example of this need involves the so called 1 Lioy PJ. Exposure science: a view of the past and milestones for the future. Environ “Unconventional Natural Gas Development (UNG)” or hydrofrack- Health Perspect 2010; 118: 1081–1090. ing, commonly referred to as “fracking.” A review of the situation 2 Lioy P, Weisel C Exposure Science: Basic Principles and Applications. Academic was recently published by Adgate et al. in 2014.18 In addition, in Press—Elsevier, 2014. December 2013 the NRDC conducted a workshop on monitoring 3 Ott WR Human exposure assessment: the birth of a new science. J Expo Anal needs.19 To be transparent, UNG activities have been around Environ Epidemiol 1995; 5:449–472. for years, but not on the scale being pursued today, or 4 NRC. Risk Assessment in the Federal Government: Managing the Process. The National Academies Press, 1983. projected in the years ahead. As with PM, after completing fi fi 5 NRC. Science and Decisions: Advancing Risk Assessment. The National Academies UNG contaminant identi cation, one of the rst orders of Press, 2009. business should be to conduct well-defined exposure studies in 6 NRC. Review of EPA's Integrated Risk Information System (IRIS) Process. The National communities and workplaces following the determination of Academies Press, 2014.

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